Disorders of growth are among the most common problems related to the skeletal system in children. Sulfated glycosaminoglycan (GAGS) biosynthesis in cartilage has been found to be markedly depressed in disorders associated with decreased growth and increased in disorders associated with increased growth. Multiple growth factors (somatomedins) have been isolated and shown to increase GAGS biosynthesis as measured by sulfate uptake. The specific sites of action of these polypeptide growth factors in the regulation of GAGS biosynthesis, however, have not been determined. The objectives, of this research project, therefore, will be: 1) to delineate the specific sites of action of known growth factors in the regulation of GAGS biosynthesis, 2) to study the effect of other growth hormones as well as that of drugs on somatomedin stimulated GAGS biosynthesis. To accomplish this objective, we will validate our assay for each of the growth factors employed by determining its effect on the total protein, GAGS, DNA, RNA, and collagen using our established embryonic chick cartilage system. We will then proceed to delineate the effect of growth factors (somatomedins) on specific steps in the GAGS biosynthetic pathway: a) their effect on the acceptor protein moiety and b) their effect on various glycosyltransferase enzymes (i.e. xylosyl-, galactosyl-, glucuronyl-, sulfo-, and acetyl glycosamino-transferase). Finally, we will investigate the effect of known inhibitors of protein, DNA, RNA, and GAGS synthesis in terms of their specific site of interference within the GAGS biosynthetic pathway. These studies are designed to establish the site of metabolic action of various growth factors in the control of skeletal growth. They should provide us with a better understanding as to how various hormones and drugs facilitate or inhibit growth processes in children.